1. Field of the Invention
The present invention relates to nanostructured sensor systems for measurement analytes, for example by measurement of variations of electrical properties of nanostructure elements in response to an analyte, such as biomolecule, organic and inorganic species, including environmentally and medically relevant volatiles and gases, such as NO, NO2, CO2, NH3, H2, CO and the like. Certain embodiments of nanostructured sensor systems are configured for measurement of medically important gases in breath. Examples are described relating to the measurement of endogenous nitric oxide in breath, such as for the monitoring or diagnosis of asthma and other pulmonary conditions.
2. Description of Related Art
The measurement of carbon dioxide levels in respiration is a standard procedure during intensive care and anesthesia and is a primary tool in the diagnosis and management of respiratory function. In addition to the measurement of CO2, medical breath analysis and monitoring may employ measurements of many other chemical species to improve diagnosis and patient care. In general, exhaled breath has a composition which is distinct from inspired air. Compounds are either removed from inspired air (e.g., oxygen as O2 is absorbed and metabolized) or added to exhaled breath (e.g., CO2, H2O). In addition, treatment compounds (e.g., anesthetic agents) may be added to inspired air for inhaled administration, and may be detected in exhaled breath.
Although the substantial portions of exhaled breath include N2, O2, CO2, water vapor and other atmospheric constituents (e.g., argon and the like), many volatile organic and inorganic chemical species which are produced by metabolic processes within the body are released in exhaled breath (often in only trace amounts). Such metabolic species often have medical significance. For example, nitric oxide (NO), nitrogen dioxide (NO2), other nitrogen-containing compounds, sulfur-containing compounds, hydrogen peroxide, carbon monoxide, hydrogen, ammonia, ketones, aldehydes, esters, alkanes, and other volatile organic compounds may be present in exhaled breath. Medical conditions related to such metabolic exhaled breath constituents include tissue inflammation (e.g. asthma), immune responses (e.g. to cancer cells or bacteria), metabolic problems (e.g. diabetes), digestive processes, liver problems, kidney problems, heart problems, gum disease, halitosis, blood component levels, and other physiological conditions.
NO detection in breath is a proven marker for airway inflammation (as well as for other tissue inflammation, immune responses, and other conditions). Therefore, the ability to measure NO as an exhaled breath parameter, for example as fractional exhaled nitric oxide (FeNO), is a valuable tool for diagnosis, monitoring, and managed treatment of asthma and other disorders. See, for example, U.S. Pat. No. 6,010,459 entitled “Method and apparatus for the measurement of components of exhaled breath in humans”, which is incorporated by reference. However, medical systems for the measurement of NO suffer from generally the same limitations as capnograph devices, e.g., high cost, weight and complexity.
CO2 detection in breath has been used as an indicator of perfusion and heart function as well as ventilator effectiveness. In addition, CO2 is useful, by itself or in combination with other measurements, in diagnosing and monitoring airway status and pulmonary function. For example, see U.S. Pat. No. 6,648,833 entitled “Respiratory analysis with capnography”, which is incorporated by reference.
It has also been proposed to monitor medical conditions, such as asthma, using detection of more than one metabolic species, for example considering both NO and CO2 in exhaled breath. For example, see US Published Application No. 2003-0134,427 entitled “Method and apparatus for determining gas concentration”; and C. Roller et al., “Simultaneous NO and CO2 measurement in human breath with a single IV-VI mid-infrared laser”, Optics Letters (2002) Vol. 27, No. 2, pgs. 107-109; each of which is incorporated by reference.
There are several different conventional technologies for sensing NO gas for medical breath analysis applications. In laser detection, a laser may be tuned to a frequency which is selectively absorbed by NO. A photo detector then detects the transmission of laser light through a sample column, the degree of absorption by the gas being related to NO concentration. NO may also be detected by such methods as chemiluminescence, and other optical detection methods. See, for example, U.S. Pat. No. 6,038,913 entitled “Device for determining the levels of NO in exhaled air”; US Published Application No. 2003-0134,427, entitled “Method and apparatus for determining gas concentration”, and US Published Application No. 2004-0017,570 entitled “Device and system for the quantification of breath gases”, each of which is incorporated by reference. However, each of the conventional NO detection strategies suffer limitations in equipment size, weight, cost and/or operational complexity that limit their use for a low-cost, patent-portable.